Abstract This thesis explores the integration of work practice and system design in deliberating upon how to increase the sensitivity of system design towards everyday work practice. The attempt to make work practice visible and intelligible for system design necessarily relates to two very different bodies of knowledge: the actual work activities and knowledge of practitioners, and what is considered relevant information for requirements analysis in system design. The strategy of this work comprises the integration of ethnographically informed study of work practice and participatory design by drawing on the longitudinal fieldwork of studying technologically mediated radiology work and promoting work practice based participatory design interventions into technology projects in the clinic of radiology. The adopted theoretical attitude of interweaving construction and reconstruction necessitates questioning and reconfiguring some of the taken-for-granted assumptions of disciplinary dichotomies and conventional frames of reference both with regard to ethnographic traditions focused on current practices as well as technology-centered and future-oriented system design. Radiology, with its ongoing and complex transition from film-based to digitally mediated work, has provided the concrete setting for thinking about the relations between researcher, designer and work practice practitioner in an attempt to find ways in which to sensitise system design towards everyday work practice. Establishing the relevance between ethnographic findings of work and design specifications requires a reformulation of work practice that appreciates the everyday fluency of work practice and recognises the endogenous change for the needs of system design. The possibilities of extending the multivoiced expertise prevalent in participatory design with an explicit interest on emic-etic views and knowledges inherent within ethnographic traditions is explored through reflecting on the changing researcher knowledge and location. The reflections are also used in developing a tool for work practice oriented participatory design and in constructing the role of participant interventionist. Through mutual exploration and constructive collaboration of ethnographic and participatory design traditions as well as scrutiny of actual design sessions, the dimensions of analytic distance, horizon of work practice transformations and situated generalisation are put forward as general interactions of work practice sensitive participatory design.